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NSAIDs

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NSAIDS con contribute to kidney damage

By David Dunaief, M.D.

Dr. David Dunaief

Last week, I wrote that the CDC estimates as many as 15 percent of U.S. adults have chronic kidney disease (CKD) and that roughly 90 percent of them don’t know they have it (1). This includes about 50 percent of people with a high risk of kidney failure in the next five years.

How is this possible? CKD is tricky because it tends to be asymptomatic, initially. Only in the advanced stages do symptoms become distinct, although there can be vague symptoms in moderate stages such as fatigue, malaise and loss of appetite. Those at highest risk for CKD include patients with diabetes, high blood pressure and those with first-degree relatives who have advanced disease. But those are only the ones at highest risk.

Why does CKD matter?

Your kidneys function as efficient little blood filters. They remove wastes, toxins and excess fluid from the body. In addition, they play roles in controlling blood pressure, producing red blood cells, maintaining bone health, and regulating natural chemicals in the blood. When they’re not operating at full capacity, the consequences can be heart disease, stroke, anemia, infection and depression — among others. According to the U.S. Preventive Services Task Force and the American College of Physicians, those who are at highest risk should be screened including patients with diabetes or hypertension (2)(3).

Slowing CKD progression

Fortunately, there are several options available, ranging from preventing CKD with specific exercise to slowing the progression with lifestyle changes and medications.

Exercise helps – even walking

The results of a study show that walking reduces the risk of death and the need for dialysis by 33 percent and 21 percent respectively (4). Even more intriguing, those who walked more often saw greater results. So, the participants who walked one-to-two times a week had a significant 17 percent reduction in death and a 19 percent reduction in kidney replacement therapy, while those who walked at least seven times per week experienced a more impressive 59 percent reduction in death and a 44 percent reduction in the risk of dialysis. There were 6,363 participants with an average age of 70, and they were followed for an average of 1.3 years.

How much protein to consume?

When it comes to CKD, more protein is not necessarily better, and it may even be harmful. In a meta-analysis of 17 Cochrane database studies of non-diabetic CKD patients who were not on dialysis, results showed that the risk of progression to end-stage kidney disease, including the need for dialysis or a kidney transplant, was reduced 36 percent in those who consumed a very low-protein diet, rather than a low-protein or normal protein diet (5).

Reducing sodium consumption

Good news! In a study, results showed that a modest sodium reduction in our diet may be sufficient to help prevent proteinuria (protein in the urine) (6). Here, less than 2000 mg was shown to be beneficial, something all of us can achieve.

Medications have a place

We routinely give certain medications, ACE inhibitors or ARBs, to patients who have diabetes to protect their kidneys. What about patients who do not have diabetes? ACEs and ARBs are two classes of anti-hypertensives — high blood pressure medications — that work on the kidney systems responsible for blood pressure and water balance (7). Results of a study show that these medications reduced the risk of death significantly in patients with moderate CKD. Most of the patients were considered hypertensive.

However, there was a high discontinuation rate among those taking the medication. If you include the discontinuations and regard them as failures, then all who participated showed a 19 percent reduction in risk of death, which was significant. However, if you exclude discontinuations, the results are much more robust with a 63 percent reduction. To get a more realistic picture, this result, including both participants and dropouts, is probably close to what will occur in clinical practice unless the physician is a really good motivator or has very highly motivated patients.

Should you be taking NSAIDs?

Non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen and naproxen, have been associated with CKD progression and with kidney injury in those without CKD (1). For those on ACE inhibitors or ARBs, NSAIDs can also interfere with their effectiveness. Talk to your doctor about your prescription NSAIDs and any other over-the-counter medications you are taking.

Takeaways

You don’t necessarily have to rely on drug therapies to protect your kidneys, and there is no down-side to lifestyle modifications. Lowering sodium modestly, walking frequently, and lowering your protein consumption may all be viable options, with or without medication. Discuss with your physician whether you need regular screening. High-risk patients with hypertension and diabetes should definitely be screened; however, those with vague symptoms of lethargy, aches and pains might benefit from screening, as well.

References: (1) cdc.gov/kidneydisease (2) uspreventiveservicestaskforce.org (3) aafp.org. (4) Clin J Am Soc Neph-rol. 2014;9(7):1183-9. (5) Cochrane Database Syst Rev. 2020;(10):CD001892. (6) Curr Opin Nephrol Hypertens. 2014;23(6):533-540. (7) J Am Coll Cardiol. 2014;63(7):650-658.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

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NSAIDs and acetaminophens are not risk-free

By David Dunaief, M.D.

Dr. David Dunaief

What’s in your medicine cabinet? If you’re like most people, you have your typical “go-tos” for pain relief, fever or inflammation. You might have aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) and acetaminophen (Tylenol). 

Familiar NSAIDs include ibuprofen (Advil, Motrin) and naproxen sodium (Aleve). Over 70 million prescriptions for NSAIDs are written each year in the U.S., and Americans consume more than 30 billion doses, once over-the-counter (OTC) use is factored in (1).

According to a poll of these regular users of OTC NSAIDs, a substantial number — 60 percent — were unaware of their dangerous side effects (2). Acetaminophen is used frequently, as well. On a weekly basis, one quarter of Americans take it. Unfortunately, many think of these drugs as relatively benign. In fact, I find that until I specifically ask about their use, most patients don’t include them in a list of their medications.

NSAID risks

Unfortunately, NSAIDs, according to the Centers for Disease Control and Prevention, are responsible for 7,600 deaths annually and 10 times that number in hospitalizations (3). These are not medications that should be taken lightly. 

NSAIDs increase the risk of several maladies, including heart attacks, gastrointestinal bleeds, exacerbation of diverticular disease, chronic arrhythmias (abnormal heartbeats) and erectile dysfunction. In some instances, the cardiovascular effects can be fatal.

These risks prompted the FDA to strengthen the warning labels on non-aspirin NSAID labels, advising that those taking NSAIDs should immediately seek medical attention if they experience chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech (4).

Adverse side effects of NSAIDs

In a case control study using the UK Primary Care Database, chronic users of NSAIDs between ages 40 and 89 had a significantly increased risk of a serious arrhythmia (abnormal heartbeat) called atrial fibrillation (5).

Interestingly, chronic users were defined as patients who took NSAIDs for more than 30 days. Those patients who used NSAIDs more than 30 days had a 57 percent increased risk of atrial fibrillation. A Danish study reinforces these results after the first month of use (6). This is not very long to have such a substantial risk. For patients who used NSAIDs longer than one year, the risk increased to 80 percent. 

Caution should be used when prescribing NSAIDs or when taking them OTC. Atrial fibrillation is not an easy disease to treat.

NSAIDs also increase the risk of mortality in chronic users. Older patients who have heart disease or hypertension (high blood pressure) and are chronic NSAIDs users are at increased risk of death, according to an observational study (7). Compared to those who never or infrequently used them over about 2.5 years, chronic users had a greater than twofold increase in death due to cardiovascular causes. High blood pressure was not a factor, since the chronic users actually had lower blood pressure. Yet I have seen with my patients that NSAID use can increase blood pressure. 

Is acetaminophen better?

Acetaminophen does not cause gastrointestinal bleeds, arrhythmias and deaths due to cardiovascular events that NSAIDs can. However, the Food & Drug Administration announced in 2011 that acetaminophen should not exceed 325 mg every four to six hours when used as a prescription combination pain reliever (4). The goal is to reduce and avoid severe injury to the liver, which can cause liver failure. 

There is an intriguing paradox with acetaminophen: Hospitals typically dispense regular-strength 325-mg doses of the drug, whereas OTC doses frequently are found in extra-strength 500-mg tablets, and often the suggested dose is two tablets, or 1 gram. At the FDA’s request, Tylenol lowered its recommended daily dosage for extra strength Tylenol to no more than 3 grams a day to lower the risk of liver damage.

I have patients who have exceeded this, thinking that, because it is OTC, this is “safe.” Unfortunately, this is not true and can be dangerous.

The FDA’s recommendations for limiting the dose result from a conglomeration of data. For instance, one study that showed acute liver failure was due primarily to unintentional overdoses of acetaminophen (8). Accidental overdosing is more likely to occur when taking acetaminophen at the same time as a combination sinus, cough or cold remedy that also contains acetaminophen. OTC and prescription cold medications can contain acetaminophen.

Of course, if you already suffer from liver damage or disease, you should consult with your physician before taking any medications.

In order to be aware of potentially adverse events, you have to be your own best advocate and read labels. Remember to tell your physician if you are taking OTC medications.

If you are a chronic user of NSAIDs or acetaminophen because of underlying inflammation, you may find an anti-inflammatory diet, which is usually plant-based, is an effective alternative.

References:

(1) Medscape.com, 2021 Oct 21 (emedicine.medscape.com/article/816117-overview). (2) J Rheumatol. 2005;32;2218-2224. (3) Annals of Internal Medicine, 1997;127:429-438. (4) fda.gov (5) Arch Intern Med. 2010;170(16):1450-1455. (6) BMJ 2011;343:d3450. (7) Am J Med. 2011 Jul;124(7):614-620. (8) Am J Gastroenterol. 2007;102:2459-2463. 

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com. 

There are serious side effects of NSAIDs and Tylenol

Dr. David Dunaief

Most of us keep a few key items in our medicine cabinets. In addition to aspirin, among these are usually NSAIDs (non-steroidal anti-inflammatory drugs) and acetaminophen (Tylenol). We often use them for relief of pain, fever or inflammation. Familiar NSAIDs include ibuprofen (Advil, Motrin) and naproxen sodium (Aleve). It is estimated that more than 17 million people use NSAIDs on a daily basis. According to a poll of these regular users of over-the-counter (OTC) NSAIDs, a substantial number — 60 percent — were unaware of their dangerous side effects (1).

Acetaminophen is used frequently, as well. On a weekly basis, one quarter of Americans take it. 

We think of these drugs as relatively benign. In fact, I find that unless I specifically ask about their use, most patients don’t include them on a list of their medications on a patient registration form. 

NSAIDs: The statistics

Unfortunately, NSAIDs, according to the Centers for Disease Control and Prevention, are responsible for 7,600 deaths annually and 10 times that number in hospitalizations (2). These are not medications that should be taken lightly. NSAIDs increase the risk of several maladies, including erectile dysfunction, heart attacks, gastrointestinal bleeds, exacerbation of diverticular disease and chronic arrhythmias (abnormal heartbeats). In some instances, the cardiovascular effects can be fatal. 

NSAIDs: Studies demonstrating adverse side effects

In a case control (epidemiologic, retrospective) study using the UK Primary Care Database, chronic users of NSAIDs have a significantly increased risk of a serious arrhythmia (abnormal heartbeat) called atrial fibrillation (3). Patients were between 40 and 89 years of age. 

Interestingly, chronic users were defined as patients who took NSAIDs for more than 30 days. Those patients who used NSAIDs more than 30 days had a 57 percent increased risk of atrial fibrillation. A Danish study reinforces these results after the first month of use (4). This is not very long to have such a substantial risk. For patients who used NSAIDs longer than one year, the risk increased to 80 percent. Caution should be used when prescribing NSAIDs or when taking them OTC. Atrial fibrillation is not an easy disease to treat.

NSAIDs also increase the risk of mortality in chronic users. Older patients who have heart disease or hypertension (high blood pressure) and are chronic NSAIDs users are at increased risk of death, according to an observational study (5). Compared to those who never or infrequently used them over about 2.5 years, chronic users had a greater than twofold increase in death due to cardiovascular causes. High blood pressure was not a factor, since the chronic users actually had lower blood pressure. Yet I have seen with my patients that NSAIDs can increase blood pressure. 

Is acetaminophen the answer?

Acetaminophen does not cause gastrointestinal bleeds, arrhythmias and deaths due to cardiovascular events that NSAIDs can. However, the Food & Drug Administration announced in 2011 that acetaminophen should not exceed 325 mg every four to six hours when used as a prescription combination pain reliever (6). The goal is to reduce and avoid severe injury to the liver, which can potentially cause liver failure. 

There is an intriguing paradox with acetaminophen: Hospitals typically dispense regular-strength 325-mg doses of the drug, whereas OTC doses frequently are found in extra-strength 500-mg tablets, and often the suggested dose is two tablets, or 1 gram. Patients should not take more than 4 grams a day to lower their risk of liver damage. The 4-gram amount sounds like a significant quantity, but it translates into two pills of extra-strength Tylenol every six hours.

I have patients who have taken three pills at one time thinking that, since it is OTC, exceeding the dose is okay. Unfortunately, this is not true. 

The FDA’s recommendations for limiting the dose result from a conglomeration of data. For instance, one study that showed acute liver failure was due primarily to unintentional overdoses of acetaminophen (7). Accidental overdosing is more likely to occur when taking acetaminophen at the same time as a combination sinus, cough or cold remedy that also contains acetaminophen. Over-the-counter cold medications can contain acetaminophen. 

In order to be aware of potentially adverse events, you have to be your own best advocate and read labels. Remember to tell your physician if you are taking OTC medications. If you are a chronic user of NSAIDs because of underlying inflammation, you may find an anti-inflammatory diet, which is usually plant-based, is an effective alternative.

References: 

(1) J Rheumatol. 2005;32;2218-2224. (2) Annals of Internal Medicine, 1997;127:429-438. (3) Arch Intern Med. 2010;170(16):1450-1455. (4) BMJ 2011;343:d3450. (5) Am J Med. 2011 Jul;124(7):614-620. (6) FDA.gov. (7) Am J Gastroenterol. 2007;102:2459-2463. 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

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Diet choices and vitamin B3 have surprising effects

By David Dunaief

Dr. David Dunaief

Warmer weather is finally upon us, we now have long, sunny days and, soon, the beach. However, longer sun exposure does increase the risk of skin cancer. Melanoma is the most serious skin cancer, but fortunately it is not the most common. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) are more prevalent, in that order. Here, we will focus on these two types.

The incidences of these skin cancers are very difficult to pin down because they are not readily reported. However, most of us either know someone who has had these types of skin cancer or have had them ourselves. There were roughly 3.5 million nonmelanoma skin cancer treatments in the U.S. in 2006, with the number of treatments increasing 77 percent from 1992 to 2006 (1). SCC and BCC outcomes diverge, with the former having a higher risk of metastases compared to the latter, which tends to grow much slower (2).

These skin cancers may present in different ways. BCC may have a bump that is pearly, waxy, light-colored or pink or flesh-colored or brown. It may bleed, ooze and crust, but may not heal, and can be sunken in the middle (3). SCC has the appearance of a growing nodule. It may also be scaly or crusty and may have flat reddish patches. It may be a sore that also may not heal. It is found on sun-exposed areas, more commonly the forehead, hands, lower lip and nose (3). Interestingly, SCC develops over years of gradual UV sun exposure, while BCC develops more like melanoma through intense multiple sporadic burns (4).

The more well-known risks for these types of skin cancer include sun exposure (UV radiation), light skin, age, ethnicity and tanning beds (2). But there are other risk factors, such as manicures. There are also ways to reduce risk with sunscreen reapplied every two hours, depending on what you are doing, but also NSAIDs (nonsteroidal anti-inflammatory drugs) and even vitamin B3. Let’s look at the research.

Beyond skin cancer

Though nonmelanoma skin cancers (NMSCs) have far less potential to be deadly, compared to melanoma, there are other risks associated with them. In the CLUE II cohort study of over 19,000 participants, results show something very disturbing: A personal history of NMSC can lead to other types of cancer throughout the body (5). The increased risk of another type of cancer beyond NMSC is 103 percent in those with BCC and 97 percent in those with SCC, both compared to those who did not have a personal history of NMSC.

Tanning beds — No surprise

We know that tanning beds may be a cause for concern. Now the FDA has changed the classification of tanning beds from low to moderate risk and requires a warning that they should not be used by those under the age of 18 (6). The catch is that this does not have teeth; if tanning salons ignore the new rules, there is no punishment.

However, in a prospective (forward-looking) study, results show that people’s responses to warnings depended on how the warnings were framed (7). Compared to the text-only FDA warning requirement, graphic warnings that emphasized the risks of skin cancer were more likely to help people stop using tanning beds, whereas graphic warnings that demonstrated the positive benefits of not using these devices had no effects. So you may have to scare the daylights out of those in their teens and early twenties.

A recent study showed that drying lamps used after a manicure could lead to skin cancer.

Manicure risk, really?

I am told women and some men love manicures. Manicures cannot possibly be dangerous, right? Not so fast. It is not the actual manicure itself, but rather the drying process that poses a risk. In a prospective study, results show that drying lamps used after a manicure may increase the risk of DNA damage to the skin, which could lead to skin cancer, though the risk is small per visit (8).

There were a lot of variables. The shortest number of visits to increase the risk of skin cancer was eight, but the intensity of the UVA irradiance varied considerably in 17 different salons. The median number of months it took to have carcinogenic potential with exposure was around 35, or roughly three years. The authors recommend either gloves or suntan lotion when using these devices, although both seem to be somewhat impractical with wet nails. It’s best to let your nails dry naturally.

Vitamin B3 to the rescue

Many vitamins tend to disappoint when it comes to prevention. Well, hold on to your hat. This may not be the case for vitamin B3. In the Australian ONTRAC study, the results showed that vitamin B3 reduced the risk of developing NMSC by 23 percent, compared to those who took a placebo (9). Even better was the fact that SCC was reduced by 30 percent.

The most interesting part about this study is that these results were in high-risk individuals who had a personal history of NMSC. The participants were given B3 (nicotinamide 500 mg) twice daily for one year.

After the patients discontinued taking B3, the benefits dissipated within six months. The study was on the small side, including 386 patients with two or more skin cancer lesions in the last five years, with a mean of eight lesions. The side effects were minimal and did not include the flushing (usually neck and facial redness) or headaches seen with higher levels of niacin, another derivative. The caveat is that this study was done in Australia, which has more intense sunlight. We need to repeat the study in the U.S. Nicotinamide is not expensive, and it has few side effects.

NSAIDs as beneficial?

Results have been mixed previously in terms of NSAIDs and skin cancer prevention. However, a more recent meta-analysis (nine studies of varying quality, with six studies considered higher quality) showed that especially nonaspirin NSAIDs reduced the risk of SCC by 15 percent compared to those who did not use them (10).

Diet — The good and the bad

In terms of diet studies, there have been mixed positive and neutral results, especially when it comes to low-fat diets. These are notoriously difficult to run because the low-fat group rarely remains low fat. However, in a prospective dietary study, results showed that effects on skin cancer varied depending on the foods. For those who were in the highest tertile of meat and fat consumption, compared to those in the lowest tertile, there was a threefold increased risk of a squamous cell cancer in those who had a personal history of SCC (11). But what is even more interesting is that those who were in the highest tertile of vegetable consumption, especially green leafy vegetables, experienced a 54 percent reduction in skin cancer, compared to those in the lowest consumption tertile.

Thus, know that there are modifiable risk factors that reduce the risk of nonmelanoma skin cancer and don’t negatively impact your enjoyment of summer. There may be easy solutions to help prevent recurrent skin cancer, as well, that involve both medication and lifestyle modifications.

References: (1) Arch Dermatol. 2010;146(3):283. (2) uptodate.com. (3) nih.gov. (4) Br J Cancer. 2006;94(5):743. (5) J Natl Cancer Inst. 2008;100(17):1215-1222. (6) federalregister.gov. (7) Am J Public Health. Online June 11, 2015. (8) JAMA Dermatol. 2014;150(7):775-776. (9) ASCO 2015 Annual Meeting: Abstract 9000. (10) J Invest Dermatol. 2015;135(4):975-983. (11) Am J Clin Nutr. 2007;85(5):1401.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.